Long-term protection of hematopoiesis against the cytotoxic effects of multiple doses of nitrosourea by retrovirus-mediated expression of human O6-alkylguanine-DNA-alkyltransferase

A human O6-alkylguanine-DNA-alkyltransferase (ATase) cDNA-containing retrovirus was used to infect murine long-term primary bone marrow cultures. High levels of ATase expression were obtained, and colony- forming cells of the granulocyte-macrophage lineage from the cultures transduced with the human ATase retrovirus were three times more resistant to the alkylating agent, N-methyl-N-nitrosourea (MNU), than control cultures. Furthermore, expression of the human ATase protected long-term hematopoiesis, measured as the output of progenitor cells to the nonadherent fraction of the culture, against the cytotoxic effects of repeated exposures to MNU. These results clearly show that a human ATase cDNA-containing retrovirus can be used to infect long-term primary bone marrow cultures and that this attenuates their sensitivity to nitrosoureas.     

输尿管硬镜在尿路疾病治疗中的应用

目的:探讨输尿管硬镜在尿路疾病治疗中的应用效果。方法:对1000例尿路结石、输尿管及尿道狭窄、输尿管息肉、梗阻、异物存留等患者,均以输尿管硬镜配合其他设备进行治疗。结果:肾内结石34例治愈率76.5%,输尿管结石、膀胱及尿道结石治愈率为94.5%～99.8%;泌尿道狭窄治愈率66.7%～75%;33例泌尿道异物取出率97%。结论:基层医院在尿路疾病治疗中,根据病变的不同部位,将输尿管硬镜灵活配合现有并不高档的设备,同样可以取得较好的微创手术效果。     

Effects of the bone morphogenetic protein binding protein spp24 (secreted phosphoprotein 24 kD) on the growth of human lung cancer cells

Bone morphogenetic proteins (BMPs) and transforming growth factor‐beta (TGF‐β) contribute to the growth of some skeletal metastases through autocrine stimulation. Secreted phosphoprotein 24 kDa (spp24) has been shown to bind to both BMP‐2 and TGF‐β and to markedly inhibit the osteogenic properties of rhBMP‐2. We hypothesized that the addition of spp24 would sequester autocrine growth factors (especially BMP‐2) and reduce tumor growth in a system (A549 human non‐small cell lung cancer cell line) where autocrine stimulation by BMP‐2 is known to be important. A549 cells were injected into two sites (subcutaneous and intraosseus) in SCID mice with and without the co‐injection of BMP‐2 and spp24. Tumor growth after 8 weeks was assessed through gross examination, radiological imaging, and histological analysis. Spp24 attenuated the tumor growth enhancing effects of rhBMP‐2 and reduced the tumor growth when added to tumor cells that were not treated with BMP‐2. We conclude that spp24 can reduce A549 cell tumor growth in both soft tissue and intraosseus environments. We hypothesize that the mechanism for this inhibition is interruption of autocrine stimulation through the sequestration of BMP‐2. Spp24 can be developed into a therapeutic agent that can be employed in clinical situations where the inhibitions of BMPs and related proteins is advantageous. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1712–1718, 2011     

Impact of biventricular and left ventricular pacing on hemodynamics and left ventricular dyssynchrony compared with right ventricular pacing in the early postoperative period following cardiac surgery

Objectives

The aims of this study were to test the hypotheses that in the postoperative period following corrective surgery for congenital heart defects: (i) atrio-right ventricular (RA-RV) pacing decreases cardiac output (CO) compared with right atrial (RA) pacing, (ii) atrio-biventricular (RA-BiV) and left ventricular (RA-LV) pacing improves CO compared with RA-RV pacing.

Study design

Prospective observational study.

Patients

Children 0-2 years of age referred for surgery of congenital heart defects were studied during intrinsic rhythm and atrial, atrio-right ventricular, atrio-left ventricular and atrio-biventricular pacing. CO, extrapolated from mean systolic aortic velocity (MSAV), and left ventricular dyssynchrony were assessed using transthoracic echocardiography.

Results

RA-RV pacing induced a significant decrease in CO (MSAV 0.52 ± 0.19 m/s to 0.46 ± 0.16 m/s, p = 0.01) and a significant increase in LV dyssynchrony (8.7 ± 7.9 ms to 33 ± 21 ms, p = 0.001). RA-BiV pacing induced a significant increase in CO (MSAV 0.46 ± 0.16 m/s to 0.52 ± 0.18 m/s, p = 0.01) and a significant decrease in LV dyssynchrony (33 ± 21 ms to 7 ± 4 ms, p = 0.0003) compared with RA-RV pacing. RA-LV pacing induced a significant decrease in LV dyssynchrony (33 ± 21 ms to 9 ± 7 ms, p = 0.0007) without a significant improvement of CO compared with RA-RV pacing.

Conclusions

RA-BiV pacing improves CO compared with RA-RV pacing in the early postoperative period following pediatric cardiac surgery. This improvement is related to a reduction in left ventricular dyssynchrony.     

Impact of medical and surgical intervention on survival in patients with cholangiocarcinoma

AIM:To examine surgical and medical outcomes for patients with cholangiocarcinoma using a populationbased cancer registry.METHODS:Using the California Cancer Registry’s Cancer Surveillance Program,patients with intrahepatic cholangiocarcinoma treated in Los Angeles County from 1988 to 2006 were identified and evaluated for clinical and pathologic factors and therapies received(surgery,radiation,and chemotherapy).The surgical cohort was further categorized into three treatment groups:patients who received adjuvant chemotherapy,adjuvant chemoradiation,or underwent surgery alone(no chemotherapy or radiation administered).Survival was assessed by Kaplan-Meier method;and Cox proportional hazard modeling was used in multivariate analysis.RESULTS:Of 825 patients,60.2% received no treatment.Of the remaining 328 patients,18.5% chemotherapy only,7.4% chemoradiation,and 13.8% underwent surgery.More male patients underwent surgical resection(P = 0.004).Surgical patients were younger than the patients receiving chemotherapy or chemoradiation(P < 0.001).Of the surgical cohort(n = 114),60.5% underwent surgery alone while 39.5% underwent surgery plus adjuvant therapy(chemotherapy n = 20;chemoradiation,n = 21)(P < 0.001).Median survival for all patients in the study was 6.6 mo.Median survival was highest for patients who underwent surgery(23 mo),whereas both chemotherapy(9 mo) and chemoradiation(8 mo) alone were each less effective(P < 0.001).By multivariate analysis,extent of disease,receipt of surgery,and administration of chemotherapy(with/without surgery) were independent predictors of overall survival.CONCLUSION:This study demonstrates that surgery is a critical treatment modality.Multimodality treatment has yet to be standardized,but play a role in optimal therapy for cholangiocarcinoma.     

Influence of pain and urinary symptoms on quality of life in young men with chronic prostatitis-like symptoms

BACKGROUND: Our aims in the present study were to estimate the influences of pain and urinary symptoms on quality of life, and to determine which of these two variables has the most predictive power with respect to quality of life in young men with chronic prostatitis-like symptoms. METHODS: Chronic prostatitis-like symptoms were measured by the National Institutes of Health-Chronic Prostatitis Symptom Index. Of the 28,841 men aged 20 years who lived in the study community, 18,495 men (a response rate 64.1%) agreed to participate in the study. A total of 1057 men who complained of symptoms indicative of chronic prostatitis were included in the study. The influences of pain and urinary symptoms on quality of life were determined using logistic regression analysis. The receiver operating characteristic (ROC) curve was used to estimate the predictive ability of each of these variables with respect to quality of life. RESULTS: Results from multivariate analysis showed that both pain and urinary symptoms were associated with an increased likelihood of impaired quality of life, although pain contributed more to a reduced quality of life than urinary symptoms. Relative to men who experienced mild pain, men who experienced moderate pain had a 3.9-fold risk of poor quality of life (odds ratio [OR], 3.87; 95% confidence interval [CI], 2.86-5.23; P < 0.001) and those who experienced severe pain had a 15.7-fold risk of reduced quality of life (OR, 15.68; 95% CI, 6.59-37.35; P < 0.001). Moderate urinary symptoms were associated with a 1.4-fold risk of bother (OR, 1.41; 95% CI, 1.01-1.99; P < 0.001) and severe urinary symptoms were associated with 2.4-fold risk (OR, 2.39; 95% CI, 1.37-4.12; P < 0.001), relative to mild urinary symptoms. Comparison of the effects of pain and urinary symptoms showed that pain severity had the most predictive power for bother, quality of life, and quality-of-life impact. The areas under the ROC curves for bother, quality of life, and quality-of-life impact were 71.3%, 69.3% and 72.5%, respectively. CONCLUSION: Urinary symptoms and pain might be associated with an increased likelihood of impaired quality of life in young men with chronic prostatitis-like symptoms. In addition, our findings suggest that pain severity is the most influential variable for determining quality of life in this population.